Any device intended to control hemodynamics of the circulatory system in patients with cardiac injury or disease requires a mechanism for efficiently assessing the patient's hemodynamic status. The performance of the heart's left ventricle is a primary determinant of hemodynamic status. The measurement of blood pressure within the left ventricle would accurately provide a parameter directly related to left ventricular function. However, there is no practical means for measuring pressure within the left ventricle. The measurement of blood pressure within the peripheral systemic circulatory system provides some assessment of left ventricular performance. Unfortunately, these measurements are inaccurate due to the variability in blood pressure resulting from peripheral influences such as differences in the contractility of peripheral blood vessels. More accurate information regarding left ventricular function is provided by combining blood pressure measurements from the peripheral circulatory system with those from either of the right chambers of the heart.
The heart may be more accurately modelled as a constant volume pump than as a constant pressure pump. Therefore, a better criterion for assessing the hemodynamic status of the circulatory system is provided by measurements of the volume of blood flow pumped from the heart, rather than blood pressure determinations. In a constant volume system, the parameters of end diastolic volume, ventricular filling, cardiac output, and the contractility of the heart muscle accurately describe the pumping performance of the heart. Each of these parameters is directly related to cardiac contractility. A systolic time interval is a characteristic measurement of a time interval separating one or more electrical and mechanical cardiac events. The measurement of appropriate systolic time intervals, in combination with an analysis of timed blood flow volumes, allows the accurate estimation of some of the aforementioned hemodynamic parameters.
The contractility of the heart muscle determines the forces and pressures generated within the heart. As the heart muscle contracts, the pressure increases in the heart chamber. In turn, the changes in pressure control the opening and closing of heart valves and thereby regulate the blood flow from one chamber into another and from the left ventricle into the systemic and pulmonary circulatory systems. The timing of these electrical and mechanical events reflects the pressures generated within the heart. Cardiac contractility and intraventricular pressures and forces are difficult to measure. In contrast, the relative timing of heart valve opening and closing events and the correlation of these mechanical events with cardiac electrical polarization events is a measurable quantity which is expressed as a systolic time interval parameter. By determining cardiac contractility in this manner, an apparatus can assess whether the cardiovascular system is adequately supporting the needs of the body. Myocardial contractility, as derived in the form of systolic time intervals, is appropriate for usage as a control parameter in a closed-loop hemodynamic control system. Some measurements, which are known in the prior art, are less directly related to the hemodynamic functionality of the heart.
The fundamental advantage of a hemodynamic control method based on the measurement of cardiac contractility or its direct corollary, cardiac output, and its usage to control a cardiac assist device is illustrated by the three-phase relationship between cardiac output and pacing rate shown in a report by J. L. Wessale et al., entitled "Cardiac Output Versus Pacing Rate At Rest And With Exercise In Dogs With AV Block", PACE, Vol.11, page 575 (1988). At low pacing rates (first phase), the cardiac output increases proportional to pacing rate. At some point (second phase), further increases in pacing rate cause the cardiac output to rise only slightly, if at all. At still higher pacing rates (third phase), further increases will cause the cardiac output to diminish. The width of the second phase is considered an indication of the pumping capacity of the ventricles and the health of the heart. Rate-responsive pacemakers cannot determine the phase of the cardiac output/pacing rate relationship for a given pacing rate without measuring cardiac output.
Some prior art devices measure physiological and physical parameters other than cardiac contractility, and regulate hemodynamics accordingly. Hemodynamic control in such devices is performed in an open-loop, rather than a closed-loop, manner since the relationship between the actual hemodynamic state, as defined by the cardiac contractility, and the measured control parameter is not known. The response of such devices is less directly related to the response of the heart since the hemodynamic status is characterized by a parameter related only secondarily to such status. The prior art includes a number of pacemakers, called rate-responsive pacemakers, each of which adjusts the heart rate of a patient based on a measurement acquired using a sensor to derive a parameter related in some manner to metabolic demand. Cardiac electrical activity (either stimulated or natural), body motion, respiration and temperature are examples of such parameters for assessing metabolic demand in a cardiac control device.
The method of determining metabolic demand using each of these measured parameters requires the previous correlation of the parameter with cardiac output by means of clinical experimentation. These correlation relationships are subject to wide variability from patient to patient and from one test to the next in an individual patient. More importantly, each of the parameters is subject to influences from physiological and physical sources which are unrelated to cardiac output and metabolic demand. The influences affecting these measurements are poorly understood and difficult to characterize. Furthermore, since the secondarily-related metabolic indicator pacing rates do not take the actual output from the heart into account, they may actually hinder the ability of the heart to meet the necessary metabolic demand, as illustrated in the aforementioned report by Wessale. As a consequence, all sensing and control means using a control parameter which is secondarily related to cardiac output and metabolic demand suffer from the inability to assess the hemodynamic status of the cardiovascular system.
Dual chamber heart pacers have been developed in order to generate sequential atrial and ventricular pacing pulses which closely match the physiological requirements of a patient. A conventional dual chamber heart pacer, as disclosed in U.S. Pat. No. 4,429,697 to Nappholz et al., dated Feb. 7, 1984, and entitled "Dual Chamber Heart Pacer with Improved Ventricular Rate Control," includes atrial and ventricular beat sensing and pulse generating circuits. It is known that the detection of a ventricular beat or the generation of a ventricular pacing pulse initiates the timing of an interval known as the V-A delay. If an atrial beat is not sensed prior to expiration of the V-A delay interval, then an atrial pacing pulse is generated. Following the generation of an atrial pacing pulse, or a sensed atrial beat, an interval known as the A-V delay is timed. If a ventricular beat is not sensed prior to the expiration of the A-V delay interval, then a ventricular pacing pulse is generated. With the generation of a ventricular pacing pulse, or the sensing of a ventricular beat, the V-A delay timing starts again. This patent describes how the V-A delay timing interval may be divided into three parts; the atrial refractory period, the Wenkeback timing window, and the P-wave synchrony timing window. It outlines the importance of controlling rate in order to maintain synchrony between the atrium and the ventricle. The patent does not, however, address the issue of sensing the metabolic demand of the patient and distinguishing between high atrial rates due to pathological tachycardia and high atrial rates expected when the patient exercises. The dual chamber pacer, under the influence of atrial control, may correctly set a high heart rate when it senses heightened electrical activity resulting from normal physical exertion. When the same sensing system detects a heightened electrical activity arising from a pathological tachycardia episode, having similar electrical frequency and amplitude characteristics, it will incorrectly elevate the heart rate, endangering the health of the patient.
In other examples, it is known in the prior art to electrically sense and measure natural or evoked (stimulated) cardiac potentials and analyze these signals to derive parameters such as Q-T intervals or evoked potential depolarization gradients. These are disclosed, respectively, in Rickard's U.S. Pat. No. 4,527,568, entitled "Dual Chamber Pacer with Alternative Rate Adaptive Means and Method", issued Jul. 9, 1985, and in Callaghan's U.S. Pat. No. 4,766,900, entitled "Rate Responsive Pacing System using the Integrated Cardiac Event Potential", issued Aug. 30, 1988. The efficacy of this sensing and control method depends largely on the signal amplitude and timing characteristics of the cardiac repolarization waveform, which is erratically influenced by many physiological, pharmacological and electrical phenomena. These phenomena are poorly understood, frequently leading to an unstable control behavior in devices using such sensing and control methods.
It is known in the prior art of cardiac pacemakers to control pacing rate based on the determination of cardiac output. In one example (Salo et al. in U.S. Pat. No. 4,686,987, entitled "Biomedical Method and Apparatus for Controlling the Administration of Therapy to a Patient in Response to Changes in Physiological Demand", issued Aug. 18, 1987), the device estimates cardiac output using intracardiac impedance measurements between two spaced electrodes disposed within the right ventricular cavity. This apparatus measures the blood impedance by injecting subthreshold (non-stimulating) electrical current pulses into the heart through one electrode and detecting the current at the second electrode. From changes in impedance, this device estimates changes in left ventricle volume by integrating the measurements over time, leading to the estimation of cardiac output. Unfortunately, inherent in the usage of impedance as a control parameter is the lack of a reliable relationship between impedance and actual cardiac output sought as the basis for control. When a device measures impedance using only two electrodes, gross volume approximation errors occur which are magnified during the integration process leading to the determination of cardiac output. In addition, since the electrodes are necessarily implanted into the right rather than the left ventricle (the left ventricle is not available for access) and the estimate of left ventricular volume in this manner is very crude and inaccurate, the cardiac output estimate derived using impedance techniques is highly susceptible to cumulative errors in each of the integration steps. Furthermore, extraneous influences on the impedance signal such as noise from respiration, changes in the patient's posture, and electrical interference produce a large noise signal and lead to further errors.
One recent development in cardiac monitoring and control is the implantable pressure sensor. Schroeppel describes one example of such control in U.S. Pat. No. 4,708,143, entitled "Method for Controlling Pacing of a Heart in Response to Changes in Stroke Volume", issued Nov. 24, 1987. Existing cardiac control systems using pressure sensors measure atrial and venous pressures to determine absolute and relative pressure changes during the cardiac cycle, to measure time intervals between electrophysiological phenomena, and to derive an estimate of cardiac output or stroke volume from these measurements. Pressure sensors, even when used in the most effective manner, are implantable only in locations which allow direct measurement of pressure within the right heart, rather than in the left ventricle. Measurements from the right heart poorly estimate the true hemodynamic state of the patient.
It is known in the art for a cardiac pacemaker to measure a systolic time interval for the purpose of using this parameter to control cardiac pacing rate. Such devices sense cardiac electrical events from intracardiac electrograms, sense cardiac mechanical events in various manners, and correlate the timing of these mechanical and electrical events to determine systolic time intervals, including pre-ejection period and left ventricular ejection time. In turn, these devices use the systolic time interval to determine a rate control parameter. None of these prior art devices detect mechanical cardiac events using Doppler ultrasound measurement techniques. In U.S. Pat. No. 4,708,143, discussed previously, a pacemaker uses piezoelectric sensing to measure ejection time. From ejection time, the pacemaker estimates stroke volume and correlates the stroke volume estimate with heart rate.
In U.S. Pat. No. 4,719,921 to Chirife, entitled "Cardiac Pacemaker Adaptive to Physiological Requirements", issued Jan. 19, 1988, a pacemaker uses a blood pressure sensor to detect variations in the blood pressure waveform in the peripheral vascular system or right ventricle. The pacemaker analyzes mechanical cardiac events measured from the blood pressure waveform to determine pre-ejection intervals and set the heart rate from these intervals. Because it is not possible to measure blood pressure in either the arterial system or the left ventricle, this technique of controlling cardiac pacing from the pre-ejection period measurement is subject to large errors which degrade the pacemaker's rate responsive behavior.
In U.S. Pat. No. 4,773,401 to Citak et al., entitled "Physiological Control of Pacemaker Rate using Pre-ejection Interval as the Controlling Parameter", issued Sep. 27, 1988, a pacemaker senses impedance measurements from a multi-electrode lead, positioned within the right ventricle, to measure the time from the QRS-complex of the intracardiac electrogram to the first positive crossing of the impedance signal average. The pacemaker uses this time to estimate pre-ejection period for the purpose of controlling pacing rate. The impedance measurement is susceptible to noise which produces large errors in measured time intervals. Unfortunately, to correctly set the pacing rate, the time interval measurement must be very precise.
Each of the prior art techniques for estimating systolic time intervals and relating such intervals to myocardial contractility are inaccurate and complex. The primary source of inaccuracy is the lack of access to direct measurements within the left ventricle.
It is also known in the art to use noninvasive Doppler ultrasound techniques to measure the maximum blood flow velocity in the aorta or pulmonary artery and to determine cardiac output as a product of the time average mean velocity and the estimated cross-sectional area. One such usage of Doppler ultrasound techniques is described by Colley et al. in U.S. Pat. No. 4,319,580, entitled "Method for Detecting Air Emboli in the Blood in an Intracorporeal Blood Vessel", issued Mar. 16, 1982. Devices use these prior art ultrasound techniques to monitor cardiovascular hemodynamics by measuring cardiac output and stroke volume, but do not use these measurements to control cardiac functions.